NANJING, China, Aug 28, 2026
InxMed Co., Ltd. announced the publication in The Lancet Oncology of clinical results evaluating ifebemtinib (IN10018) in combination with garsorasib (D-1553) in patients with previously treated KRAS G12C-mutant metastatic colorectal cancer (CRC). The findings come from a Phase Ib/II clinical trial evaluating the efficacy and safety of the all-oral, chemotherapy-free combination in KRAS G12C-mutant solid tumors. In the randomized portion of the study, the combination demonstrated a confirmed objective response rate of 38.9% compared with 16.7% for garsorasib alone, while also showing favorable trends in progression-free and overall survival. The publication provides clinical evidence supporting further investigation of FAK inhibition combined with KRAS G12C inhibition as a potential strategy for addressing treatment resistance in metastatic colorectal cancer.
Combination Therapy Shows Antitumor Activity in KRAS G12C CRC
The colorectal cancer cohort included both a single-arm study and randomized study, enrolling patients with previously treated KRAS G12C-mutant metastatic CRC. In the single-arm portion, 15 patients received oral ifebemtinib 100 mg once daily plus garsorasib 600 mg twice daily, with 14 patients evaluable for response. The confirmed objective response rate was 46.7% in the full population and 50.0% among evaluable patients, while median progression-free survival was 6.9 months and median overall survival was 14.3 months. In the randomized portion, 36 patients were assigned equally to receive the combination or garsorasib monotherapy. The combination produced a confirmed ORR of 38.9% versus 16.7% with garsorasib alone, representing an absolute improvement of 22.2 percentage points. Median PFS was 7.7 months with the combination compared with 4.0 months for monotherapy, corresponding to a hazard ratio of 0.48, while median overall survival was not estimable in the combination group versus 7.5 months with garsorasib alone.
FAK Inhibition Targets KRAS Therapy Resistance
The development strategy is based on research indicating that KRAS G12C inhibition alone can activate adaptive resistance mechanisms within tumor cells and their surrounding microenvironment. According to InxMed, translational research showed that KRAS G12C inhibition can trigger hyperactivation of the FAK–YAP signaling pathway and promote fibrogenesis in the tumor microenvironment, supporting tumor-cell survival. Ifebemtinib is an orally available, highly selective focal adhesion kinase (FAK) inhibitor designed to interfere with this pathway. By combining FAK inhibition with KRAS G12C inhibition, the company aims to sensitize tumor cells to KRAS-targeted treatment and potentially extend treatment response. The approach is particularly relevant in metastatic colorectal cancer, where KRAS G12C mutations occur in approximately 3–4% of patients and treatment resistance remains a significant clinical challenge. The company described the study as the first clinical investigation, to its knowledge, evaluating a FAK inhibitor in combination with a KRAS G12C inhibitor in KRAS G12C-mutant solid tumors.
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Phase III Development Planned for Ifebemtinib Combination
The combination also demonstrated a manageable safety profile across 33 patients who received ifebemtinib plus garsorasib. Treatment-related adverse events were reported in 97% of patients, with most events being Grade 1 or 2 and Grade 3 treatment-related adverse events occurring in 30% of patients. No Grade 4 treatment-related adverse events, treatment-related deaths or treatment-related adverse events leading to study-drug discontinuation were reported. The most common treatment-related adverse events included diarrhea, proteinuria and nausea. Based on the clinical findings, InxMed said the results support advancing the combination into a pivotal study. The company has submitted an Investigational New Drug (IND) application in China for a Phase III trial comparing ifebemtinib plus garsorasib with investigators’ choice of standard therapy in previously treated metastatic colorectal cancer harboring a KRAS G12C mutation. Ifebemtinib is being developed globally by InxMed and has demonstrated safety and tolerability in more than 700 subjects, with the company pursuing additional combinations involving RAS inhibitors, immune checkpoint inhibitors and antibody-drug conjugates.
Source: InxMed press release
